3x23
From Proteopedia
Radixin complex
Structural highlights
Function[RADI_MOUSE] Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane. [MMP14_HUMAN] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.[1] [2] Publication Abstract from PubMedMembrane type 1-matrix metalloproteinase (MT1-MMP) is a key enzyme involved in tumor cell invasion by shedding their cell-surface receptor CD44 anchored with F-actin through ezrin/radixin/moesin (ERM) proteins. We found the cytoplasmic tail of MT1-MMP directly binds the FERM domain of radixin, suggesting F-actin-based recruitment of MT1-MMP to CD44 for invasion. Our crystal structure shows that the central region of the MT1-MMP cytoplasmic tail binds subdomain A of the FERM domain, and makes an antiparallel beta-beta interaction with beta2A-strand. This binding mode is distinct from the previously determined binding mode of CD44 to subdomain C. We showed that radixin simultaneously binds both MT1-MMP and CD44, indicating ERM protein-mediated colocalization of MT1-MMP and its substrate CD44 and anchoring to F-actin. Our study implies that ERM proteins contribute toward accelerated CD44 shedding by MT1-MMP through ERM protein-mediated interactions between their cytoplasmic tails. MT1-MMP recognition by ERM proteins and its implication in CD44 shedding.,Terawaki S, Kitano K, Aoyama M, Mori T, Hakoshima T Genes Cells. 2015 Oct;20(10):847-59. doi: 10.1111/gtc.12276. Epub 2015 Aug 20. PMID:26289026[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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